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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Stagnation Region Heat Transfer Augmentation at Very High Turbulence Levels

A database for stagnation region heat transfer has been extended to include heat transfer measurements acquired downstream from a new high intensity turbulence generator. This work was motivated by gas turbine industry heat transfer designers who deal with heat transfer environments with increasing Reynolds numbers and very high turbulence levels. The new mock aero-combustor turbulence generator produces turbulence levels which average 17.4%, which is 37% higher than the older turbulence generator. The increased level of turbulence is caused by the reduced contraction ratio from the liner to the exit. Heat transfer measurements were acquired on two large cylindrical leading edge test surfaces having a four to one range in leading edge diameter (40.64 cm and 10.16 cm). Gandvarapu and Ames [1] previously acquired heat transfer measurements for six turbulence conditions including three grid conditions, two lower turbulence aero-combustor conditions, and a low turbulence condition. The data are documented and tabulated for an eight to one range in Reynolds numbers for each test surface with Reynolds numbers ranging from 62,500 to 500,000 for the large leading edge and 15,625 to 125,000 for the smaller leading edge. The data show augmentation levels of up to 136% in the stagnation region for the large leading edge. This heat transfer rate is an increase over the previous aero-combustor turbulence generator which had augmentation levels up to 110%. Note, the rate of increase in heat transfer augmentation decreases for the large cylindrical leading edge inferring only a limited level of turbulence intensification in the stagnation region. The smaller cylindrical leading edge shows more consistency with earlier stagnation region heat transfer results correlated on the TRL (Turbulence, Reynolds number, Length scale) parameter. The downstream regions of both test surfaces continue to accelerate the flow but at a much lower rate than the leading edge. Bypass transition occurs in these regions providing a useful set of data to ground the prediction of transition onset and length over a wide range of Reynolds numbers and turbulence intensity and scales.

20 FOSSIL-FUELED POWER PLANTS↗
DOE OSTI2015

Video Fact Sheets: Everyday Advanced Materials

What are Advanced Materials? Ames Laboratory is behind some of the best advanced materials out there. Some of those include: Lead-Free Solder, Photonic Band-Gap Crystals, Terfenol-D, Aluminum-Calcium Power Cable and Nano Particles. Some of these are in products we use every day.

36 MATERIALS SCIENCE↗
DOE OSTI2015

Observations of 14 CO 2 in ecosystem respiration from a temperate deciduous forest in Northern Wisconsin

We show that the 14 CO 2 composition of plant and soil respiration can be used to determine the residence time of photosynthetically fixed carbon before it is released back to the atmosphere. To estimate the residence time of actively cycled carbon in a temperate forest, we employed two approaches for estimating the Δ 14 CO 2 of ecosystem respiration (Δ 14 C-R eco ) at the Willow Creek AmeriFlux site in Northern Wisconsin, USA. Our first approach was to construct nighttime Keeling plots from subcanopy profiles of Δ 14 CO 2 and CO 2 , providing estimates of Δ 14 C-R eco of 121.7‰ in June and 42.0‰ in August 2012. These measurements are likely dominated by soil fluxes due to proximity to the ground level. Our second approach utilized samples taken over 20 months within the forest canopy and from 396 m above ground level at the nearby LEF NOAA tall tower site (Park Falls, WI). In this canopy-minus-background approach we employed a mixing model described by Miller and Tans (2003) for estimating isotopic sources by subtracting time-varying background conditions. For the period from May 2011 to December 2012 the estimated Δ 14 C-R eco using the Miller-Tans model was 76.8‰. Together, these Δ 14 C-R eco values represent mean R eco carbon ages of approximately 1–19 years. We also found that heterotrophic soil-respired Δ 14 C at Willow Creek was 5–38‰ higher (i.e., 1–10 years older) than predicted by the Carnegie-Ames-Stanford Approach global biosphere carbon model for the 1 × 1 pixel nearest to the site. Finally, this study provides much needed observational constraints of ecosystem carbon residence times, which are a major source of uncertainty in terrestrial carbon cycle models.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Strong regional atmospheric 14 C signature of respired CO 2 observed from a tall tower over the midwestern United States

Radiocarbon in CO 2 ( 14 CO 2 ) measurements can aid in discriminating between fast (<1 year) and slower (>5–10 years) cycling of C between the atmosphere and the terrestrial biosphere due to the 14 C disequilibrium between atmospheric and terrestrial C. However, 14 CO 2 in the atmosphere is typically much more strongly impacted by fossil fuel emissions of CO 2 , and, thus, observations often provide little additional constraints on respiratory flux estimates at regional scales. Here we describe a data set of 14 CO 2 observations from a tall tower in northern Wisconsin (USA) where fossil fuel influence is far enough removed that during the summer months, the biospheric component of the 14 CO 2 budget dominates. We find that the terrestrial biosphere is responsible for a significant contribution to 14 CO 2 that is 2–3 times higher than predicted by the Carnegie-Ames-Stanford approach terrestrial ecosystem model for observations made in 2010. This likely includes a substantial contribution from the North American boreal ecoregion, but transported biospheric emissions from outside the model domain cannot be ruled out. The 14 CO 2 enhancement also appears somewhat decreased in observations made over subsequent years, suggesting that 2010 may be anomalous. Furthermore, with these caveats acknowledged, we discuss the implications of the observation/model comparison in terms of possible systematic biases in the model versus short-term anomalies in the observations. Going forward, this isotopic signal could be exploited as an important indicator to better constrain both the long-term carbon balance of terrestrial ecosystems and the short-term impact of disturbance-based loss of carbon to the atmosphere.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2011

Improved efficiency in blue phosphorescent organic light emitting devices using host materials of lower triplet energy than the phosphorescent blue emitter

Data from a series of phosphorescent blue organic light emitting devices OLEDs with emissive layers consisting of either CBP:6% Firpic or mCP:6% FIrpic show that the triplet energy of the hole and electron transport layers can have a larger influence on the external quantum efficiency of an operating OLED than the triplet energy of the host material. These results are important and insightful given the commonly held view that host materials for phosphorescent OLEDs must have a triplet energy higher than that of the emitter in order to obtain high external quantum efficiency (EQE). A new host material, 4-(di-ptolylaminophenyl)diphenylphosphine oxide (DHM-A2), which has a triplet energy less than that of FIrpic is also reported. OLEDs fabricated using DHM-A2 show improved performance (lower drive voltage and higher external quantum efficiency) over OLEDs using 4- (diphenylphosphoryl)-N,N-diphenylaniline (HMA1), a high performance ambipolar DHM-A2 analogue with a triplet energy greater than FIrpic. Our results suggest modified design rules for the development of new, high performance host materials., ames, more focus can be placed on molecular structures that provide good charge transport (i.e., ambipolarity for charge balance) and good molecular stability (for long lifetimes). This improved understanding provides additional flexibility in order to generate OLEDs with lower operating voltage and longer lifetime, while still providing high EQE.

36 MATERIALS SCIENCE↗
DOE OSTI2016

Comparing the Performance of Three Land Models in Global C Cycle Simulations: A Detailed Structural Analysis: Structural Analysis of Land Models

Land models are valuable tools to understand the dynamics of global carbon (C) cycle. Various models have been developed and used for predictions of future C dynamics but uncertainties still exist. Diagnosing the models’ behaviors in terms of structures can help to narrow down the uncertainties in prediction of C dynamics. In this study three widely used land surface models, namely CSIRO’s Atmosphere Biosphere Land Exchange (CABLE) with 9 C pools, Community Land Model (version 3.5) combined with Carnegie-Ames-Stanford Approach (CLM-CASA) with 12 C pools and Community Land Model (version 4) (CLM4) with 26 C pools were driven by the observed meteorological forcing. The simulated C storage and residence time were used for analysis. The C storage and residence time were computed globally for all individual soil and plant pools, as well as net primary productivity (NPP) and its allocation to different plant components’ based on these models. Remotely sensed NPP and statistically derived HWSD, and GLC2000 datasets were used as a reference to evaluate the performance of these models. Results showed that CABLE exhibited better agreement with referenced C storage and residence time for plant and soil pools, as compared with CLM-CASA and CLM4. CABLE had longer bulk residence time for soil C pools and stored more C in roots, whereas, CLM-CASA and CLM4 stored more C in woody pools due to differential NPP allocation. Overall, these results indicate that the differences in C storage and residence times in three models are largely due to the differences in their fundamental structures (number of C pools), NPP allocation and C transfer rates. Our results have implications in model development and provide a general framework to explain the bias/uncertainties in simulation of C storage and residence times from the perspectives of model structures.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Aerodynamic measurements on wind turbines

This article reviews the aerodynamic measurement programs on wind turbines that have been performed in the last decades. It is largely based on results from four projects carried out under auspices of the International Energy Agency (IEA), which are denoted as IEA Tasks 14, 18, 20, and 29. The aim of these projects was to collect and analyze aerodynamic measurements on five field facilities (IEA Tasks 14 and 18), the National Renewable Energy Laboratory Phase VI turbine placed in the large NASA Ames wind tunnel (IEA Task 20), and the Mexico turbine placed in the Large Low Speed Facility of the German Dutch Wind tunnel DNW (IEA Task 29). Other experimental programs with an important aerodynamic content are touched upon as well. Research areas for which these measurements have led to important progress are identified. The progress is illustrated with analyses on these experiments. It is shown that detailed aerodynamic measurements are an absolute necessity for the validation and improvement of wind turbine design codes, where it is also concluded that the amount of measurement data which has been produced until now is still far too limited.

17 WIND ENERGY↗
DOE OSTI2013

Systematic Review of Infrapopliteal Drug-Eluting Stents: A Meta-Analysis of Randomized Controlled Trials

IntroductionDrug-eluting stents (DES) have been proposed for the treatment of infrapopliteal arterial disease. We performed a systematic review to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing infrapopliteal DES.Materials and MethodsPubMed (Medline), EMBASE (Excerpta Medical Database), AMED (Allied and Complementary medicine Database), Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), online content, and abstract meetings were searched in September 2012 for eligible RCTs according to the preferred reporting items for systematic reviews and meta-analyses selection process. Risk of bias was assessed using the Cochrane Collaboration's tool. Primary endpoint was primary patency defined as absence of {>=}50 % vessel restenosis at 1 year. Secondary outcome measures included patient survival, limb amputations, change of Rutherford-Becker class, target lesion revascularization (TLR) events, complete wound healing, and event-free survival at 1 year. Risk ratio (RRs) were calculated using the Mantel-Haenszel fixed effects model, and number-needed-to-treat values are reported.ResultsThree RCTs involving 501 patients with focal infrapopliteal lesions were analyzed (YUKON-BTX, DESTINY, and ACHILLES trials). All three RCTs included relatively short and focal infrapopliteal lesions. At 1 year, there was clear superiority of infrapopliteal DES compared with control treatments in terms of significantly higher primary patency (80.0 vs. 58.5 %; pooled RR = 1.37, 95 % confidence interval [CI] = 1.18-1.58, p < 0.0001; number-needed-to-treat (NNT) value = 4.8), improvement of Rutherford-Becker class (79.0 vs. 69.6 %; pooled RR = 1.13, 95 % CI = 1.002-1.275, p = 0.045; NNT = 11.1), decreased TLR events (9.9 vs. 22.0 %; pooled RR = 0.45, 95 % CI = 0.28-0.73, p = 0.001; NNT = 8.3), improved wound healing (76.8 vs. 59.7 %; pooled RR = 1.29, 95 % CI = 1.02-1.62, p = 0.04; NNT = 5.9), and better overall event-free survival (72.2 vs. 57.3 %; pooled RR = 1.26, 95 % CI = 1.10-1.44, p = 0.0006; NNT = 6.7). Conclusion. DES for focal infrapopliteal lesions significantly inhibit vascular restenosis and thereby improve primary patency, decrease repeat procedures, improve wound healing, and prolong overall event-free survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Biosynthesis, Microstructural Characterisations and Investigation of In-Vitro Mutagenic and Eco-Toxicological Response of a Novel Microbial Exopolysaccharide Based Biopolymer

A modified microbial polysaccharide based biopolymer has been investigated as a potential candidate towards development of sustainable biomaterials and bioplastics. An in-depth study was carried out to biosynthesize, characterize and assess any possible mutagenic potential and ecotoxicity of the microbial polysaccharide biopolymer. Microstructural investigations using confocal microscopy, Fourier transform (FT)-Raman depth profile mapping and scanning electron microscopy (SEM) of the biosynthetically modified polysaccharide revealed internal structural perturbations, as well as occlusion of granular pores by extraneous materials. The Raman 3D mapping depth profile along with time-of-flight (MALDI-TOF) mass spectrometry also indicated important structural and surface modifications, which could be correlated to the production of microbial exopolysaccharides and secondary metabolites. The study then looked into any possible genetic mutation and ecological risks associated with the biosynthetically modified polysaccharide through the investigation of genotoxicity and ecotoxicity. The genotoxicity study was carried out through bacterial reverse gene mutation (Ames) test by using two different strains (TA98 and TA100) of bacteria. The results did not indicate any mutagenic effect against either of the strains used for the biopolymer samples and was found to be genotoxically safe. Ecotoxicity tests, carried out using bioluminescent bacteria Vibrio fisheri further indicated no ecotoxicity within the given experimental conditions. The study measured the half maximal effective concentration (EC50) to cause a 50% decrease in the light output of the bacteria, a measure of ecotoxicological response of the biopolymer. Overall, results from this study indicated that the novel biopolymer was genotoxically and ecotoxically safe, which offers immense potential for future use of this biopolymer.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Synergistic effect of microstructure and defects on the initiation of fatigue cracks in additively manufactured Inconel 718

Fatigue cracks in additively manufactured (AMed) Inconel 718 (IN-718) in machined surface condition often initiate from persistent slip bands (PSBs) unlike other popular AM alloys such as 17-4 PH stainless steel or Ti-6Al-4V, where fatigue crack initiation is exclusively from volumetric defects; therefore, a competition between PSB- vs. defect- mediated crack initiation clearly exists. To shed light on the factors governing the competition, this study investigates the characteristics of cyclic strain localization, PSB formation, and crack initiation via crystal plasticity (CP) modeling of cyclic loading on polycrystalline aggregates which are then validated by experiments. In this work, a physics-based, free slip distance (FSD) dependent slip strength evolution law is proposed, which is shown to enable the CP model to simulate the heterogeneous strain distribution in IN-718. Implementing a crack initiation criterion based on strain contrast, the locations and lives for crack initiation can also be calculated. It is shown that both FSD and resolve shear stress influence the strain localization and crack initiation behaviors. The distribution of a localization parameter calculated based on the multiplication of FSD and Schmid factor within a grain is found to correlate well with the locations of PSBs. The maximum values of the localization parameters within a microstructure are shown to correlate well with the experimentally obtained crack initiation lives. The presence of volumetric defects in IN-718 generally do not impact strain localization behavior unless their size is large compared to the grain size.

42 ENGINEERING↗
DOE OSTI2015

Systematic validation of non-equilibrium thermochemical models using Bayesian inference

The validation process proposed by Babuška et al. [1] is applied to thermochemical models describing post-shock flow conditions. In this validation approach, experimental data is involved only in the calibration of the models, and the decision process is based on quantities of interest (QoIs) predicted on scenarios that are not necessarily amenable experimentally. Moreover, uncertainties present in the experimental data, as well as those resulting from an incomplete physical model description, are propagated to the QoIs. We investigate four commonly used thermochemical models: a one-temperature model (which assumes thermal equilibrium among all inner modes), and two-temperature models developed by Macheret et al. [2], Marrone and Treanor [3], and Park [4]. Up to 16 uncertain parameters are estimated using Bayesian updating based on the latest absolute volumetric radiance data collected at the Electric Arc Shock Tube (EAST) installed inside the NASA Ames Research Center. Following the solution of the inverse problems, the forward problems are solved in order to predict the radiative heat flux, QoI, and examine the validity of these models. Our results show that all four models are invalid, but for different reasons: the one-temperature model simply fails to reproduce the data while the two-temperature models exhibit unacceptably large uncertainties in the QoI predictions.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2018

Hydrothermal synthesis of molybdenum trioxide, characterization and photocatalytic activity

Highlights: • α-MoO{sub 3} micro-belts were synthesized hydrothermally. • Micro-belts were found very rich in surface oxygen vacancies. • CR-F3BS photocatalytic degradation was promising. • The cytotoxicity and mutagenicity were reduced significantly of CR-F3BS. - Abstract: α-MoO{sub 3} micro-belts were synthesized via hydrothermal technique and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), atomic force microscopy (AFM), energy dispersive X-ray analysis (EDX) and particle size analyzer. Photo-catalytic activity was evaluated by degrading Coralene Red F3BS (CR-F3BS) dye and process variables i.e., pH, photocatalyst dose, concentration of CR-F3BS and UV exposure time were optimized using response surface methodology (RSM) under central composite design (CCD). Under optimized conditions, up to 95% degradation of CR-F3BS (10 mg/L) was achieved for 120 min UV irradiation time at pH 7 using 2.75 g/L catalyst dose. The obtained RSM model revealed a satisfactory correlation between experimental and predicted CR-F3BS degradation values. Ames and heamolytic tests revealed that the toxicity was reduced significantly as a result of photo-catalytic treatment. In view of promising efficiency, α-MoO{sub 3} micro-belts could possibly be used for the degradation of dyes in textile effluents.

36 MATERIALS SCIENCE↗
DOE OSTI2014

Survey of Evaluated Isobaric Analog States

Isobaric analog states (IAS) can be used to estimate the masses of members belonging to the same isospin multiplet. Experimental and estimated IAS have been used frequently within the Atomic Mass Evaluation (AME) in the past, but the associated set of evaluated masses have been published for the first time in AME2012 and NUBASE2012. In this paper the current trends of the isobaric multiplet mass equation (IMME) coefficients are shown. The T = 2 multiplet is used as a detailed illustration.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2022

The effects of xylo-oligosaccharides on regulating growth performance, nutrient utilization, gene expression of tight junctions, nutrient transporters, and cecal short chain fatty acids profile in Eimeria-challenged broiler chickens

A 21-d experiment was conducted to investigate the effects of xylo-oligosaccharides (XOS) on growth performance, nutrient utilization, gene expression of tight junctions, nutrient transporters, and cecal short chain fatty acids (SCFA) profile of broiler chickens challenged with mixed Eimeria spp. Two hundred fifty-two zero-day-old chicks were allocated to 6 treatments in a 3 £ 2 factorial arrangement (corn-soybean meal diets supplemented with 0, 0.5, or 1.0 g/kg XOS; with or without Eimeria challenge). Challenged groups were inoculated with a solution containing E. maxima, E. acervulina, and E. tenella oocysts on d 15. During the infection period (d 15 to d 21), there was a significant (P < 0.05) Eimeria £ XOS interaction for weight gain (WG). XOS significantly (P < 0.05) increased WG in the unchallenged birds but not in the challenged treatments. There was no significant Eimeria £ XOS interaction for N and minerals utilization responses. XOS supplementation at 0.5 g/kg tended to alleviate Eimeria-induced depression in apparent ileal digestibility of DM (P = 0.052). Challenged birds had lower (P < 0.01) AME, AMEn, and total retention of N, Ca, and P. Eimeria upregulated (P < 0.01) gene expression of tight junction proteins claudin-1, junctional adhesion molecule-2, and glucose transporter GLUT1; but downregulated (P < 0.01) the peptide transporter PepT1, amino acid transporters rBAT, CAT2, y+LAT2, and zinc transporter ZnT1. XOS alleviated (P < 0.05) Eimeria-induced claudin-1 upregulation. Eimeria decreased (P < 0.05) cecal saccharolytic SCFA acetate, butyrate, and total SCFA, but increased (P < 0.05) branched chain fatty acids isobutyrate and isovalerate. The supplementation of XOS tended to decrease the concentration of isobutyrate (P = 0.08) and isovalerate (P = 0.062). In conclusion, 0.5 g/kg XOS supplementation alleviated depression in growth performance and nutrient utilization from the Eimeria challenge. In addition, supplemental XOS reversed the gene expression changes of claudin-1, also showed the potentials of alleviating the negative cecal fermentation pattern induced by Eimeria infection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

The effects of protease, xylanase, and xylo-oligosaccharides on growth performance, nutrient utilization, short-chain fatty acids, and microbiota in Eimeria -challenged broiler chickens fed low-protein diet

A total of 392 Cobb 500 off-sex male broiler chicks were used in a 21-day experiment to study the effect of protease, xylanase, and xylo-oligosaccharides (XOS) on improving growth performance, nutrient utilization (ileal digestibility and total tract retention), gene expression of nutrient transporters, cecal short-chain fatty acids (SCFAs), and microbiota profile of broilers challenged with Eimeria spp. Chicks at 0-day old were allocated to 8 treatments in a 4 × 2 factorial arrangement: 1) corn-soybean meal diet with no enzyme (Con); 2) Con plus 0.2 g/kg protease alone (PRO); 3) Con plus 0.2 g/kg protease combined with 0.1 g/kg xylanase (PRO + XYL); or 4) Con plus 0.5 g/kg xylo-oligosaccharides (XOS); with or without Eimeria challenge. The 4 diets were formulated to be marginally low in crude protein (183 g/kg). Challenged groups were inoculated with a solution containing E. maxima, E. acervulina, and E. tenella oocysts on d 15. Eimeria depressed (P < 0.01) growth performance and nutrient utilization. Supplemental protease improved (P < 0.05) body weight gain and feed intake in the prechallenge phase (d 0-15) but had no effect during the infection period (d 15-21). There was no interaction between infection and feed supplementation for nutrient utilization. The supplementations of either PRO or XOS alone increased (P < 0.01) total tract retention of Ca and tended (P < 0.1) to improve total tract retention of N, P, AME, and AMEn. Eimeria decreased (P < 0.05) expressions of GLUT2, GLUT5, PepT1, ATP2B1, CaSR, Calbidin D28K, NPT2, and ZnT1 but increased (P < 0.01) expression of GLUT1. XOS supplementation increased (P < 0.05) ATP2B1 expression. Protease decreased (P < 0.05) isobutyrate concentration in unchallenged treatments but not in challenged treatments. Eimeria decreased (P < 0.01) cecal saccharolytic SCFAs acetate and propionate but increased (P < 0.01) branched-chain fatty acid isovalerate. The supplementation of PRO + XYL or XOS increased (P < 0.05) cecal butyrate or decreased cecal isobutyrate concentrations, respectively. PRO + XYL and XOS decreased cecal protein levels in unchallenged birds but not challenged ones. Eimeria challenge significantly (P < 0.05) decreased the microbial richness (Observed features) and diversity (Shannon index and phylogenetic diversity) and changed the microbial composition by reducing the abundance of certain bacteria, such as Ruminococcus torques, and increasing the abundance of others, such as Anaerostipes. In contrast, none of the additives had any significant effect on the cecal microbial composition. In conclusion, PRO or XOS supplementation individually improved nutrient utilization. All the additives decreased the cecal content of branched-chain fatty acids, consistent with decreased cecal N concentration, although the effects were more pronounced in unchallenged birds. In addition, none of the feed additives impacted the Eimeria-induced microbial perturbation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity

Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (± SE) Cr(VI)-reducing ability of post-meal samples (20.4 ± 2.6 μg Cr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2 ± 2.3 μg Cr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3 ± 1.9 and 25.6 ± 2.8 μg Cr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with > 70% of total reduction occurring within 1 min and 98% of reduction is achieved within 30 min with post-meal gastric fluid at pH 2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤ 180 ppm Cr(VI) for up to 90 days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water. - Highlights: • Cr(VI) reduction capacity was greater in post-meal than paired pre-meal samples. • Cr(VI) reduction was rapid, pH dependent, and due to heat stable components. • Gastric fluid attenuates the mutagenicity of Cr(VI) and reduces risk of GI cancer. • The results are useful to quantitatively evaluate the fate of ingested Cr(VI).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Naloxegol, an opioid antagonist with reduced CNS penetration: Mode-of-action and human relevance for rat testicular tumours

Naloxegol is an opioid antagonist which has been developed for the treatment of patients with opioid induced constipation. In the nonclinical safety program naloxegol was shown to have a very benign toxicity profile. In the rat, but not the mouse, 2-year carcinogenicity study a change in tumour pattern with an increase in testicular Leydig cell tumours (LCT) was observed after dosing at high (supra-pharmacological) concentrations. To establish the basis of the increase in LCT and to assess its potential relevance to humans, studies to exclude and potentially identify mode-of-action (MoA) were performed. A genotoxic mechanism was ruled out following negative results in the Ames, mouse lymphoma, and micronucleus assays. An effect on androgen metabolism was excluded since the treatment of rats with naloxegol for 14 days did not result in any induction of CYP protein levels. It was demonstrated that administration of centrally restricted opioid antagonists naloxegol or methylnaltrexone at high doses induced an increase in LH release with no clear increase in testosterone, in contrast to the centrally acting opioid antagonist naloxone, which showed marked increases in both LH and testosterone. LCT due to increased LH stimulation is common in rats but not documented in humans. Collectively, the lack of genotoxicity signal, the lack of androgen effect, the increase in LH secretion in rats, which is no considered to be relevant for LCT formation in humans, and high margins to clinical exposures, the observed increase in LCT in the rat is not expected to be clinically relevant. - Highlights: • Naloxegol elicited neuroendocrine responses in form of increased LH release. • In contrast to naloxone, naloxegol did not markedly increase testosterone. • Naloxegol treatment showed increases in rat testicular Leydig cell tumours. • A reduction in pituitary tumours was consistent with opioid antagonism. • Increase in LH mediated rat Leydig cell tumours is not relevant for patients.

60 APPLIED LIFE SCIENCES↗